The objectives of this research proposal are to determine what factors are involved in the control of utero-placental circulation, utilizing, in a chronic pregnant sheep preparation, methods which permit the direct measurement of uterine arterial blood flow and its distribution to the endometrium, myometrium, and placental cotyledons. The areas of interest include the circulatory effects of normally present endogenous compounds and pharmacologic agents frequently employed during pregnancy. By investigating the endogenous control of the utero-placental circulation, the role of placental blood flow in fetal nutrition and fetal growth might be described. This would provide insight into the pathophysiology of fetal malnutrition and, in addition, those changes naturally occuring in utero-placental blood flow during gestation and at the time of labor and delivery. The investigation of the vascular effects of commonly employed pharmacologic agents would determine which of these might be harmful to the fetus through their effect on the magnitude and distribution of uterine blood flow. Another area of interest is the possible correlation between the measurement of uterine blood flow, using the above methods, and the quantification of placental function, as determined by the rate of utilization of maternal plasma prehormone by the placenta. This would provide an indirect measurement of uterine blood flow through an evaluation of placental function and could have application in defining various physiologic aberrations during pregnancy in the human. This proposal will also address itself, by virtue of the methodology employed, to alterations in cardiac output and regional blood flows during pregnancy and following the administration of pharmacologic compounds. From this data, knowledge of changes occurring during gestation will be obtained, providing better insight into the normal cardiovascular physiology of pregnancy and its aberrations.